Genetic variants regulating the immune response improve the prediction of COVID-19 severity provided by clinical variables

Sci Rep. 2024 Sep 5;14(1):20728. doi: 10.1038/s41598-024-71476-2.

Abstract

The characteristics of the host are crucial in the final outcome of COVID-19. Herein, the influence of genetic and clinical variants in COVID-19 severity was investigated in a total of 1350 patients. Twenty-one single nucleotide polymorphisms of genes involved in SARS-CoV-2 sensing as Toll-like-Receptor 7, antiviral immunity as the type I interferon signalling pathway (TYK2, STAT1, STAT4, OAS1, SOCS) and the vasoactive intestinal peptide and its receptors (VIP/VIPR1,2) were studied. To analyse the association between polymorphisms and severity, a model adjusted by age, sex and different comorbidities was generated by ordinal logistic regression. The genotypes rs8108236-AA (OR 0.12 [95% CI 0.02-0.53]; p = 0.007) and rs280519-AG (OR 0.74 [95% CI 0.56-0.99]; p = 0.03) in TYK2, and rs688136-CC (OR 0.7 [95% CI 0.5-0.99]; p = 0.046) in VIP, were associated with lower severity; in contrast, rs3853839-GG in TLR7 (OR 1.44 [95% CI 1.07-1.94]; p = 0.016), rs280500-AG (OR 1.33 [95% CI 0.97-1.82]; p = 0.078) in TYK2 and rs1131454-AA in OAS1 (OR 1.29 [95% CI 0.95-1.75]; p = 0.110) were associated with higher severity. Therefore, these variants could influence the risk of severe COVID-19.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • Adult
  • Aged
  • COVID-19* / genetics
  • COVID-19* / immunology
  • COVID-19* / virology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Severity of Illness Index*
  • TYK2 Kinase / genetics
  • Toll-Like Receptor 7 / genetics

Substances

  • Toll-Like Receptor 7
  • TYK2 Kinase
  • 2',5'-Oligoadenylate Synthetase
  • TLR7 protein, human
  • TYK2 protein, human
  • OAS1 protein, human

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